Chronic Hepatitis B is an infectious disease prevalent throughout the world, which is caused by hepatitis B virus (HBV) and is closely associated with the occurrence of hepatocirrhosis and liver cancer. China is a high prevalence area of Hepatitis B. The results of seropidemiological survey of viral hepatitis in China from 1992 to 1995 showed that the persons carrying the viral hepatitis B surface antigen (HBsAg) in China accounted for 9.7% of the population, and it was estimated that there are 1.3×108 HBV carriers. The study on the epidemic status of viral hepatitis in China showed that the annual reported incidence rate of hepatitis B increased from 21.9/100,000 in 1990 to 53.3/100,000 in 2003, which exhibited an obvious ascending trendency (see: Wang Xiaojun, Zhang Rongzhen and Hu Yuansheng et al, Disease Surveillance, 2004, 19(8): 290-292). Chronic Hepatitis B not only seriously affects the health of human body but also imposes heavy economic burden on family and society. Chronic Hepatitis B has become one of the important public health problems in China.
Drugs for the treatment of Chronic Hepatitis B usually belong to two main classes, i.e. immunomodulators and nucleoside DNA polymerase inhibitors (Loomba R., Liang T. J., Antivir. Ther., 2006, 11(1):1-15), in which the former includes interferon-α2b (IFN-α2b, Intron A®), while the latter includes Lamivudine (EPivir-HBV®), Adefovir Dipivoxil (Hepsera®) and Entecavir (Baracluda®). Comparatively speaking, there are quite few of drugs available for the clinical treatment of Hepatitis B. Therefore, it is of great significance to carry out continuous research and development of novel and safe antiviral drugs, in particular drugs having a new mechanism of action.
Deres et al reported the dihydropyrimidine compounds substituted with a heteroaryl cyclic group, with Bay41-4109 and Bay36-5493 as representatives, which compounds can inhibit HBV replication by obstructing the formation of normal nucleocapsids. The clinical data showed that Bay41-4109 has excellent drug metabolism parameters (Deres K., Schroder C. H., Paessens A., et al, Science, 2003, 299 (5608): 893-896). The study on the action mechanism of the compounds showed that the inclination between dimers for forming a nucleocapsid is changed due to the interaction between HAP and 113-114 amino residues of a core protein, so that a unstable and expanded nucleocapsid is formed to accelerate the degradation of the core protein (Hacker H. J., Deres K., Mildenberger M., et al., Biochem. Pharmacol., 2003, 66(12): 2273-2279).
At present, there is a need to develop a novel compound that is effectively useful as an antiviral agent, in particular, as a medicament for the treatment and/or prevention of Hepatitis B.